U.S. patent application number 13/255460 was filed with the patent office on 2011-12-29 for ischemic status monitoring.
This patent application is currently assigned to ST. Jude Medical AB. Invention is credited to Michael Broome, Sven-Erik Hedberg, Stefan Hjelm, Karin Jarverud, Tomas Svensson.
Application Number | 20110319769 13/255460 |
Document ID | / |
Family ID | 42728546 |
Filed Date | 2011-12-29 |
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United States Patent
Application |
20110319769 |
Kind Code |
A1 |
Hedberg; Sven-Erik ; et
al. |
December 29, 2011 |
ISCHEMIC STATUS MONITORING
Abstract
An ischemia monitoring system has detectors for detecting the
onset of an ischemic event of a tissue in subject, the end of the
ischemic event and the end of a following recovery from the
ischemic event, respectively. A time processor determines the
duration of the ischemic event and the recovery period based on the
detected onset and end times. A status processor co-processes the
two determined time durations for the purpose of monitoring the
ischemic status of the subject and detecting any deterioration in
ischemic status for the latest ischemic event as compared to
previous ischemic events that have occurred in the subject's
tissue.
Inventors: |
Hedberg; Sven-Erik;
(Kungsangen, SE) ; Svensson; Tomas; (Stockholm,
SE) ; Broome; Michael; (Ekero, SE) ; Jarverud;
Karin; (Solna, SE) ; Hjelm; Stefan; (Balsta,
SE) |
Assignee: |
ST. Jude Medical AB
|
Family ID: |
42728546 |
Appl. No.: |
13/255460 |
Filed: |
March 13, 2009 |
PCT Filed: |
March 13, 2009 |
PCT NO: |
PCT/SE2009/000140 |
371 Date: |
September 8, 2011 |
Current U.S.
Class: |
600/481 ;
607/17 |
Current CPC
Class: |
A61B 5/1118 20130101;
A61N 1/3702 20130101; A61B 5/349 20210101; A61B 5/053 20130101;
A61B 5/7455 20130101; A61B 5/026 20130101; A61B 5/6846 20130101;
A61B 5/7405 20130101; A61B 5/1116 20130101; A61B 5/4836
20130101 |
Class at
Publication: |
600/481 ;
607/17 |
International
Class: |
A61N 1/365 20060101
A61N001/365; A61B 5/026 20060101 A61B005/026 |
Claims
1. An ischemia monitoring system comprising: an ischemia onset
detector that detects an onset of an ischemic event of a tissue of
a subject; an ischemia end detector that detects an end of said
ischemic event; a recovery end detector that detects an end of a
recovery from said ischemic event; a time processor configured to
determine an ischemic time interval of said ischemic event based on
said onset of said ischemic event detected by said ischemia onset
detector and said end of said ischemic event detected by said
ischemia end detector and to determine a recovery time interval of
said recovery based on said end of said ischemic event detected by
said ischemia end detector and said end of said recovery detected
by said recovery end detector; a memory controller that stores said
ischemic time interval and said recovery time interval determined
by said time processor or a parameter derivable from said ischemic
time interval and said recovery time interval in a connected
memory; and a status processor configured to determine an ischemic
status of said subject based on said ischemic time interval and
said recovery time interval determined by said time processor.
2. The system according to claim 1, wherein said status processor
is configured to detect a change in ischemic status of said subject
based on said ischemic time interval and said recovery time
interval determined by said time processor.
3. The system according to claim 1, wherein said ischemia onset
detector detects onset of N-1 further ischemic events of said
tissue (10), said ischemia end detector detecting the respective
ends of said N-1 further ischemic events and said recovery end
detector detects end of recovery from said N-1 further ischemic
events, where N.gtoreq.2, said system further comprising a
distribution calculator configured to calculate a statistical
distribution of said N pairs of ischemic time intervals and
recovery time intervals, and wherein said status processor is
configured to determine said ischemic status of said subject based
on a comparison of said statistical distribution calculated by said
distribution calculator with a reference statistical
distribution.
4. The system according to claim 1, further comprising: a curve
provider that provides multiple ischemia severity curves of
recovery time intervals versus ischemic time intervals, said
multiple ischemia severity curves having different recovery time
intervals for each ischemic time interval; and a curve identifier
configured to identify an ischemia severity curve among said
multiple ischemia severity curves provided by said curve provider
based on said ischemic time interval and said recovery time
interval determined by said time processor, and wherein said status
processor is configured to determine said ischemic status of said
subject based on an ischemia severity classification assigned to
said ischemia severity curve identified by said curve
identifier.
5. The system according to claim 1, further comprising an activity
sensor that determines an activity level of said subject in
connection with at least one of said ischemia onset detector
detecting said onset of said ischemic event, said ischemia end
detector detecting said end of said ischemic event and said
recovery end detector detecting said end of a recovery from said
ischemic event, wherein said status processor is arranged for
determining said ischemic status of said subject based on said
activity level determined by said activity sensor and said ischemic
time interval and said recovery time interval determined by said
time processor.
6. An implantable medical device comprising: at least one cardiac
lead; multiple electrodes arranged for collecting electrical
signals from a heart of a subject, at least one of said multiple
electrodes being arranged on said at least one cardiac lead; an
ischemia managing system connected to at least one electrode among
said multiple electrodes, and comprising an ischemia onset detector
that detects an onset of an ischemic event of a tissue of a
subject, an ischemia end detector that detects an end of said
ischemic event, a recovery end detector that detects an end of a
recovery from said ischemic event, a time processor configured to
determine an ischemic time interval of said ischemic event based on
said onset of said ischemic event detected by said ischemia onset
detector and said end of said ischemic event detected by said
ischemia end detector and to determine a recovery time interval of
said recovery based on said end of said ischemic event detected by
said ischemia end detector and said end of said recovery detected
by said recovery end detector, a memory controller that stores said
ischemic time interval and said recovery time interval determined
by said time processor or a parameter derivable from said ischemic
time interval and said recovery time interval in a connected
memory, and a status processor configured to determine an ischemic
status of said subject based on said ischemic time interval and
said recovery time interval determined by said time processor; a
treatment unit configured to generate an electric treatment signal
applicable to at least a portion of said heart via two electrodes
among said multiple electrodes; and a treatment controller
configured to control operation of said treatment unit responsive
to said status processor detecting a change in said ischemic status
of the subject.
7. The device according to claim 6, comprising an intracardiac
electrogram, (IECG) processor configured to generate an IECG based
on said electric signals collected by said multiple electrodes from
said heart, said ischemia onset detector being configured to detect
said onset of said ischemic event based on presence of a
ST-deviation in said IECG generated by said IECG processor and said
ischemia end detector being configured to detect said end of said
ischemic event based on ceasing of said ST-deviation in said IECG
generated by said IECG processor.
8. The device according to claim 7, wherein said IECG processor is
configured to generate multiple IECGs based on electric signals
collected by multiple combinations of at least two electrodes of
said multiple electrodes from said heart and to calculate a
pseudo-global IECG from said multiple IECGs; said ischemia onset
detector (110) is arranged for detecting said onset of said
ischemic event based on presence of a ST-deviation in said
pseudo-global IECG generated by said IECG processor (220); and said
ischemia end detector (120) is arranged for detecting said end of
said ischemic event based on ceasing of said ST-deviation in said
pseudo-global IECG generated by said IECG processor (220).
9. The device according to claim 6, comprising: a signal generator
configured to generate an electric signal that is applied over at
least a portion of said heart by two electrodes of said multiple
electrodes; and an impedance processor configured to determine
impedance data reflective of mechanical function of at least a
portion of said heart based on said electric signal generated by
said signal generator and a resulting electric signal collected by
two electrodes among said multiple electrodes, said recovery end
processor being configured to detect said end of said recovery from
said ischemic event based on said impedance data.
10. The device according to claim 9, wherein said impedance
processor is configured to determine said impedance data based on
said electric signal generated by said signal generator and a
resulting electric signal collected by two electrodes among said
multiple electrodes during a diastolic phase of a heart cycle of
said heart.
11. The device according to claim 6, comprising an alarm unit
configured to emit at least one of a tactile alarm and an audio
alarm in response to said status processor detecting a
deterioration in said ischemic status of said subject.
12. (canceled)
13. The device according to claim 6, wherein said treatment
controller is configured to reduce a maximum tracking rate of said
treatment unit in response to said status processor detecting a
change in said ischemic status of said subject.
14. An ischemia monitoring method comprising: detecting an onset of
an ischemic event of a tissue of a subject; detecting an end of
said ischemic event; determining an ischemic time interval of said
ischemic event based on said onset of said ischemic event and said
end of said ischemic event; detecting an end of a recovery from
said ischemic event; determining a recovery time interval of said
recovery based on said end of said ischemic event and said end of
said recovery; storing said ischemic time interval and said
recovery time interval or a parameter derivable from said ischemic
time interval and said recovery time interval; and monitoring an
ischemic status of said subject based on said ischemic time
interval and said recovery time interval.
15. The method according to claim 14, wherein said monitoring step
comprises detecting a change in ischemic status of said subject
based on said ischemic time interval and said recovery time
interval.
16. The method according to claim 14, further comprising repeating
said detecting steps and said determining steps for N-1 further
ischemic events of said tissue to obtain N pairs of ischemic time
intervals and recovery time intervals, where N.gtoreq.2, wherein
said step of detecting said change comprises: calculating a
statistical distribution of said N pairs of ischemic time intervals
and recovery time intervals; and monitoring said ischemic status of
said subject based on a comparison of said statistical distribution
with a reference statistical distribution.
17. The method according to claim 14, wherein said monitoring step
comprises: providing multiple ischemia severity curves of recovery
time intervals versus ischemic time intervals, said multiple
ischemia severity curves having different recovery time intervals
for each ischemic time interval; identifying an ischemia severity
curve of said multiple ischemia severity curves based on said
ischemic time interval and said recovery time interval; and
monitoring said ischemic status of said subject based on an
ischemia severity classification assigned to said identified
ischemia severity curve.
18. The method according to claim 14, further comprising:
determining an activity level of said subject in connection with at
least one of detecting said onset of said ischemic event, detecting
said end of said ischemic event and detecting said end of a
recovery from said ischemic event; and monitoring said ischemic
status of said subject based on said activity level and said
ischemic time interval and said recovery time interval.
Description
BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The present invention generally relates to ischemia
monitoring, and in particular to tissue ischemic status
monitoring.
[0003] 2. Description of the Prior Art
[0004] Ischemia is the lack of oxygen supply to the cells. In
animals, including humans, the underlying cause of ischemia is
typically a cardiovascular disease, where blood vessels may be
affected by arteriosclerosis. Cardiac ischemia is caused by
restriction of blood flow in the coronary arteries, e.g. due to
atherosclerosis. This reduced blood flow and the resulting lack of
oxygen to the myocytes in the heart may lead to several effects,
including hypokinesia, dyskinesia, akinesia and hibernating cells.
These various effects may in turn decrease the hemodynamic
performance of the heart, which ultimately can cause cardiac
asynchrony, worsening heart failure and further decrease in pumping
capacity.
[0005] Ischemic heart disease (IHD) is very common and
approximately 7% of the total U.S. population suffers from IHD,
with similar rates in other western countries.
[0006] IHD may be symptomatic, such as in angina pectoris, usually
occurring suddenly and causing the patient to experience severe
discomfort and pain. However, a majority of ischemic periods are
silent and therefore hard to detect and classify. Most ischemic
episodes, regardless of being symptomatic or silent, are reversible
but still influence the risk of arrhythmias and the functional
state of the heart.
[0007] U.S. Pat. No. 6,277,082 discloses detection of ischemic
biological tissue by temporarily altering the temperature of the
tissue and then monitoring the thermal profile of the tissue as it
returns to normal temperature. Not only can ischemia be detected
using such thermal profile monitoring but also the progress of
recovery of the ischemic tissue can be monitored over time.
[0008] Ischemia detection is well known in the art as exemplified
with the above-identified U.S. patent. However, there is still a
need for a technology allowing detection and monitoring of a
deterioration of ischemic status in a patient, for instance by
detecting a significant deterioration of an ischemic tissue, in
order to combat and possibly avoid complications and further
harmful effects to the tissue.
SUMMARY OF THE INVENTION
[0009] It is a general objective of the invention to provide
ischemic status monitoring in a subject.
[0010] It is a particular objective to provide a detection of a
change in ischemic status in a subject.
[0011] Briefly, in an embodiment an ischemia monitoring system
according to the invention has an ischemia onset detector arranged
for detecting the onset of an ischemic event in a tissue of a
subject, preferably a mammalian subject and more preferably a human
subject. A corresponding ischemia end detector is provided for
detecting the end of the ischemic event, which also corresponds to
the onset of a following recovery period. The ischemia monitoring
system further has a recovery end detector for detecting the end of
the recovery from the ischemic event when normal tissue function is
restored. These detected onset and end times are processed by a
time processor in order to determine an ischemic time interval
representing the duration of the ischemic event. The time processor
also determines the duration of the following recovery period in
the form of a recovery time interval. The two time intervals are
further co-processed for the purpose of monitoring the ischemic
status of the subject and detect any change, in particular
deterioration, of the ischemic burden in the tissue as compared to
previous ischemic events that have been detected and analyzed for
the subject's tissue.
[0012] In the embodiments, it is important to classify ischemic
events and monitor the ischemic status based not solely on the
duration of the ischemic event. In clear contrast, the duration of
the following recovery period is also very important to analyze
together with the ischemia event duration in order to achieve a
correct and clinically relevant ischemic status monitoring. For
instance, two ischemic events having the same duration are
different from tissue function point of view if the respective
following recovery periods have different durations.
[0013] The ischemic monitoring system can be implemented in an
implantable medical device, such as pacemaker, defibrillator or
cardioverter or indeed in a dedicated implantable ischemia
monitoring device, or be partly implemented in such an implantable
medical device and partly provided in a non-implantable data
processing device capable of conducting communication with the
implantable medical device. Alternatively, the ischemic monitoring
system is solely provided in one or more non-implanted devices.
[0014] An embodiment relates to an ischemia monitoring method that
detects onsets and ends of ischemic events and following recovery
periods for the purpose of determining the ischemic event and
recovery durations. These time durations are co-processed in order
to effect the monitoring of the subject's ischemic status.
BRIEF DESCRIPTION OF THE DRAWINGS
[0015] FIG. 1 is a schematic block diagram of an ischemia
monitoring system according to an embodiment.
[0016] FIG. 2 is a schematic block diagram of an ischemia
monitoring system according to another embodiment.
[0017] FIG. 3 is an overview of a subject having an implantable
medical device capable of communicating with a non-implanted
programmer.
[0018] FIG. 4 is a schematic block diagram of an implantable
medical device according to an embodiment.
[0019] FIG. 5 is a diagram illustrating a set of ischemia severity
curves.
[0020] FIGS. 6A to 6D are diagrams illustrating statistical
distributions of ischemic time intervals and associated recovery
time intervals.
[0021] FIGS. 7A to 7D illustrate surface ECG for healthy and
ischemic heart tissue.
[0022] FIG. 8 is a flow diagram illustrating an ischemia monitoring
method according to an embodiment.
[0023] FIG. 9 is a flow diagram illustrating an additional,
optional step of the ischemia managing method in FIG. 8.
[0024] FIG. 10 is a flow diagram illustrating an additional,
optional step of the ischemia managing method in FIG. 8.
[0025] FIG. 11 is a flow diagram illustrating an additional,
optional step of the ischemia managing method in FIG. 8.
[0026] FIG. 12 is a flow diagram illustrating an embodiment of the
monitoring step in the ischemia managing method in FIG. 8.
[0027] FIG. 13 is a diagram illustrating predefined ischemic time
and recovery time intervals for different ischemic statuses.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0028] Throughout the drawings, the same reference numbers are used
for similar or corresponding elements.
[0029] The present invention generally relates to ischemia and
ischemia monitoring in an animal subject, preferably a mammalian
subject and more preferably a human subject. Embodiments as
disclosed herein are in particular suitable for detection of a
significant change, such as deterioration or improvement, in the
ischemic status of the subject.
[0030] Ischemic status as used herein relates to an ischemic event
or attack having previously occurred in the subject's tissue. The
ischemic status is further representative of the severity of the
ischemic event in the tissue and the potential subsequent temporary
or permanent effects the ischemic event may cause in the tissue.
Thus, ischemic status can be used to denote the intensity and
burden of an ischemic event and may depend on various factors, such
as the blood supply and capacity status of the tissue during and
following the ischemic event.
[0031] In the following, embodiments will be further described in
connection with an ischemic event occurring to a subject's heart as
an illustrative tissue type. However, the embodiments are not
limited to heart tissue but also encompass other tissues and
organs, which can suffer from ischemia. In addition to hearts and
their myocytes, such potential ischemic tissue include brain
tissue, in particular nerve cells; liver tissue, e.g. hepatocytes;
pancreas and renal tissue, including cells in the renal medulla;
intestinal tissue and in particular cells in the intestinal
mucosa.
[0032] The embodiments herein allow monitoring and determining
ischemic status of the subject and can be used for detecting a
significant change in the ischemic status, such as a deterioration
or indeed an improvement in the ischemic status. In the former
case, a deterioration in ischemic status implies that a recently
occurred ischemic event is regarded has having a more severe effect
to the subject's tissue, such as heart, and the operation thereof
as compared to a previous ischemic event. Deleterious ischemic
status should be interpreted herein as an ischemic event that has a
larger risk of permanent damages to the tissue and/or larger risk
for further complications, such as myocardial infarctions in the
case of ischemic heart tissue, as compared to less severe ischemic
events. An improvement in ischemic status indicates that a recently
occurred ischemic event is regarded has having less harmful effects
to the subject's heart and its operation as compared to previously
occurred ischemic events. Embodiments as disclosed herein can
therefore trend ischemia development and such trends are followed
over time as ischemic events occur to the subject's tissue.
[0033] The ischemic status monitoring and determination is achieved
through the determination of two different time parameters relating
to an ischemic event. These time parameters include the time
interval of the ischemic event, denoted T.sub.i herein. T.sub.i,
thus, reflects the time from a detected onset of an ischemic event
up to a detected end of the ischemic event. The other time
parameter is the recovery time of the ischemic event, denoted
T.sub.r herein. T.sub.r represents the time from the detected end
of the ischemic event and thereby start of the following recovery
time up to the detected end of the recovery period. Ischemia
recovery is sometimes denoted myocardial stunning reflecting the
reversible reduction of function of heart contraction after
reperfusion not accounted for by tissue damage or reduced blood
flow. Thus, in the recovery period, the pumping performance of the
heart is altered due to the fact that the biochemistry of the heart
has to be restored following the now ended ischemic event.
[0034] In clear contrast to prior art ischemic status monitoring
solutions limited to the usage of the ischemic time interval
T.sub.i, the embodiments herein use not only T.sub.i but also the
recovery time interval T.sub.r to obtain a relevant and accurate
ischemic status monitoring and determination. Thus, the inventors
have discovered that not only the duration of an ischemic event but
also the duration of its following ischemia recovery should be used
to achieve the accurate ischemic status determination that is
needed in patient diagnosis and treatment optimization. Addition of
T.sub.r in the ischemic status monitoring allows detection of
ischemia intensity changes that negatively effects the operation of
the heart but is not necessarily associated with prolonged ischemic
time intervals. Furthermore, so-called unstable ischemic events can
be detected through the combined processing of T.sub.i and T.sub.r
as is further disclosed herein.
[0035] FIG. 1 is a schematic block diagram of an ischemia
monitoring system 100 according to an embodiment. The monitoring
system 100 includes an ischemia onset detector 110 arranged for
detecting an onset of an ischemic event of a heart in a subject.
The detection of the ischemia event onset triggers the start of an
ischemia timer or the notification of the ischemia start time
T.sub.i.sup.st by a connected time processor 140. An ischemia end
detector 120 of the ischemia monitoring system 100 investigates
whether the detected ischemia event has ceased or whether it is
still proceeding. Detection of the end of the ischemic event by the
ischemia end detector 120 causes the time processor 140 to stop the
ischemia timer or notify the ischemia end time T.sub.i.sup.e. The
time processor 140 optionally starts a recovery timer once the
ischemia end detector 120 detects the end of the ischemic event.
The ischemia monitoring system 100 also has a recovery end detector
130 arranged for monitoring the recovery progression of the heart
following the end of the ischemic event. The recovery end detector
130 in particular detects and notifies the time processor 140 of
the end of the recovery period and when correct, normal heart
function has returned. Detection of the end of the recovery
triggers the time processor 140 to stop the recovery timer or
notify the recovery end time T.sub.r.sup.e.
[0036] The time processor 140 determines an ischemic time interval
of the ischemic event based on the onset of the ischemic event
detected by the ischemia onset detector 110 and the end of the
ischemic event detected by the ischemia end detector 120. For
instance, the time processor 140 can determine the ischemic time
interval T.sub.i by reading the stopped ischemia timer.
Alternatively, the time processor 140 calculates the ischemic time
interval as T.sub.i=T.sub.i.sup.e-T.sub.i.sup.st.
[0037] Correspondingly, the time processor 140 is also arranged for
determining a recovery time interval based on the end of the
recovery detected by the recovery end detector 130 and the end of
the ischemic event detected by the ischemia end detector 120. In an
embodiment, the time processor 140 determines the recovery time
interval T.sub.r directly from the recovery timer, whereas in
another embodiment, the time processor 140 calculates the recovery
time interval as T.sub.r=T.sub.r.sup.e-T.sub.i.sup.e.
[0038] The two determined time parameters T.sub.i, T.sub.r are
preferably forwarded to a memory controller 160 having access to a
connected memory 165 implemented in the ischemia monitoring system
100 as illustrated in FIG. 1 or provided remotely but accessible to
the memory controller 160. The time parameters are either directly
forwarded from the time processor 140 to a connected status
processor 150 or is later retrieved from the memory 165 by the
memory controller 160 and provided to the status processor 150.
[0039] The status processor 150 co-processes the time parameters
for the purpose of determining an ischemic status of the subject
relating to the previously occurred and now recovered ischemic
event. Thus, the embodiments as disclosed herein involves an
ischemia monitoring system and a status processor 150 that
determines the subject's ischemic status based on both the ischemic
time interval and the associated recovery time interval.
[0040] The co-processing of T.sub.i, T.sub.r can be implemented
according to various embodiments as is shown by the following
illustrative but non-limiting examples. In general, two ischemic
events or attacks having the same duration, T.sub.i, but with two
different recovery time intervals T.sub.r typically reflect
different ischemic status. Thus, the ischemic event with the longer
recovery period is characterized to be more severe since the heart
needs a comparatively longer period of time for fully or at least
partly recovering from the ischemic attack and restoring normal or
next to normal heart operation, including blood pumping, as
compared to the ischemic event with shorter recovery period. In an
embodiment, the status processor 150 may therefore calculate a
parameter derivable from T.sub.i, T.sub.r. For instance, the
quotient between the two time parameters can be determined
T i T r or T r T i ##EQU00001##
and used as status parameter, preferably together with at least one
of T.sub.i and T.sub.r. Thus, the status processor 150 can
calculate the quotient of the two time parameters and use it
together with both or at least one of the time parameters for
determining the current ischemic status of the subject and detect
any change in the ischemic status.
[0041] A further example is to calculate the derivable parameter as
a weighted combination of T.sub.i and T.sub.r,
w.sub.iT.sub.i+w.sub.rT.sub.r, where w.sub.i and w.sub.r denotes
respective weights used for the time parameters. In an
implementation w.sub.i=w.sub.r, basically relaxing the need for any
weights, whereas in preferred implementations w.sub.i=1-w.sub.r and
0<w.sub.r<1. The actual values for these weights can be
determined and set by a physician in order to reflect the
importance of the ischemic period and the following recovery period
to the parameter and the ischemic status determination. This allows
the physician to use patient specific ischemia status
classifications that more correctly reflects the underlying
cardiovascular disease of the patient. Thus, for a first group of
patients having a certain cardiovascular disease long recovery
times with inferior cardiac pumping could be more severe as
compared to other patients that can better handle longer recovery
periods due to better general heart status prior the ischemic event
as compared to the first group of patients. The weighted sum of the
two time parameter is advantageously used in combination with one
or both of T.sub.i, T.sub.r by the status processor 150 in the
ischemic status determination.
[0042] The parameter derivable from T.sub.i, T.sub.r by the status
processor 150 may be forwarded to the memory controller 160 for
entry in the memory 165. Thus, the memory 165 could store only the
"raw" time parameter T.sub.i, T.sub.r, these time parameters and
the parameter derivable therefrom or indeed only the derived
parameter.
[0043] The status processor 150 preferably detects a change in
ischemic status of the subject based on T.sub.i, T.sub.r. In such a
case, the status processor 150 has access to one or more reference
parameters that is/are compared to the time parameters T.sub.i,
T.sub.r or the one or more parameters derivable from T.sub.i,
T.sub.r. The ischemia onset detector 110 then preferably detects
the onset of not only one but multiple, i.e. at least two,
different ischemic events occurring in the heart of the subject.
The ischemia end detector 120 and the recovery end detector 130
correspondingly detect the end of the ischemic events and the end
of the following recovery periods, respectively. This means that
the time processor 140 calculates N multiple pairs of T.sub.i,
T.sub.r for the N different ischemic events. The respective time
parameters are preferably entered in the memory 165 by the memory
controller 160 as they are determined by the time processor
140.
[0044] The status processor 150 can then calculate respective
derivable parameters, such as quotients or weighted sums, from the
N pairs of time parameters P.sub.k. The trend of these N parameters
P.sub.k is preferably followed and used by the status processor 150
for detecting a significant change in ischemic status. For
instance, the status processor 150 calculates a reference parameter
{circumflex over (P)} based on N-1 previously calculated parameter
P.sub.k, such as an average of the N-1 parameters and more
preferably a weighted average,
P ^ = 1 N - 1 k = 1 N - 1 w k P k ##EQU00002##
with
k = 1 N - 1 w k = 1 ##EQU00003##
and preferably w.sub.N-1>w.sub.N-2> . . . >w.sub.1. Such
weighted average put more weights to more recently determined time
parameters P.sub.k as compared such time parameters determined for
older ischemic events.
[0045] The status processor 150 compares the newly determined
parameter P.sub.N with the calculated average parameter {circumflex
over (P)} for the purpose of detecting a significant change in the
ischemic status of the subject. Thus, if P.sub.N differs with more
than a threshold valued from {circumflex over (P)}, the status
processor 150 concludes that a ischemic status change has been
detected and that the intensity or burden of the recently occurred
ischemic event significantly differs from the preceding N-1
ischemic events. In such a case, the status processor 150 can
trigger further actions as is described in more detail herein.
[0046] If the status processor 150 concludes that there is no
significant change in the ischemic status as determined based on
the comparison, the parameter P.sub.N is preferably entered in the
memory 165 by the memory controller. The status processor 150
optionally also updates the average parameter {circumflex over (P)}
based on P.sub.N, such as
P ^ = 1 N - 1 k = 2 N w k - 1 P k or P ^ = 1 N k = 1 N w k P k .
##EQU00004##
[0047] In an alternative approach, an optional distribution
calculator 170 is arranged in the ischemia monitoring system 100
for calculating a statistical distribution of the N pairs of
T.sub.i, T.sub.r. The distribution calculator 170 retrieves the N-1
pair(s) of T.sub.i, T.sub.r from the memory 165 and gets the most
recent T.sub.i, T.sub.r pair from the status processor 150 or
indeed from the memory 165. The status processor 150 performs the
ischemic status determination based on the comparison of the
statistical distribution from the distribution calculator from a
reference statistical distribution. This reference statistical
distribution is preferably determined by the distribution
calculator 170 based on previous pairs of T.sub.i, T.sub.r not
including the most recent T.sub.i, T.sub.r pair.
[0048] FIGS. 6A to 6D illustrate diagrams plotting pairs of
T.sub.i, T.sub.r to form a distribution of points in the T.sub.r
versus T.sub.i or T.sub.i versus T.sub.r diagrams. The distribution
of points can be regarded as a fingerprint of the ischemic status
or ischemic burden of the subject's heart. FIG. 6A represents a
baseline case, where a subject has a stable ischemic status
resulting in no significant change in ischemic time intervals and
recovery time intervals. FIG. 6B illustrates a subject having
ischemic events with comparatively longer recovery time intervals
as compared to FIG. 6A, whereas FIG. 6C illustrates a corresponding
distribution of T.sub.i, T.sub.r points for a subject with longer
ischemic time intervals. If a subject has an initial distribution
of T.sub.i, T.sub.r points as illustrated in FIG. 6A but subsequent
cardiac ischemic events result in a significant change in recovery
time interval, as in FIG. 6B, and/or a significant change in
ischemic time interval, as in FIG. 6C, the ischemic status of the
subject is changed. In both these cases, a deterioration or
worsening of the ischemic burden has occurred as compared to the
baseline condition of FIG. 6A.
[0049] FIG. 6D illustrates a subject suffering from unstable
ischemic attacks having vastly varying ischemic time intervals and
recovery time intervals. Such unstable ischemic status is believed
to be particularly severe and can be a sign of an unstable coronary
vascular disease. The ischemic status monitoring and determination
of the embodiments can therefore be used for identifying subjects
having unstable ischemic events and underlying diseases, thereby
being of particular large risk of irreversible damage to the
myocardium and myocardial infarction.
[0050] In a particular embodiment, the distribution calculator 170
calculates at least one statistical parameter representative of the
distribution of T.sub.i, T.sub.r pairs. The at least one
statistical parameter can advantageously be in the form of an
average of the respective T.sub.i, T.sub.r values and preferably
the standard deviations. In such a case, such statistical
parameters are first calculated by the distribution calculator 170
based on the previously determined T.sub.i, T.sub.r pairs stored in
the memory. The same statistical parameters are further calculated
once more but also including the T.sub.i, T.sub.r pair determined
by the time processor 140. If there is a significant change of the
mean value and/or the standard deviation, the status processor 150
determines that that the ischemic status of the subject has
changed. This embodiment is however not limited to usage of mean
value and standard deviation but can instead be used in connection
with any statistical parameter or set of parameters representative
of a distribution of multiple T.sub.i, T.sub.r pairs. Example of
such other parameters is to calculate respective quotients of
T.sub.i, T.sub.r in order to form a distribution.
[0051] FIG. 2 is a schematic block diagram of another embodiment of
the ischemia monitoring system 100 having functionality for
determining the ischemic status of a subject by means of another
technique than distribution calculations. This embodiment has a set
of so-called severity curves stored in the memory 165. These
severity curves lists or plots T.sub.r for different T.sub.i values
or vice versa. Furthermore, each such severity curve has particular
relationships between the recovery time interval and the ischemia
time intervals so that the multiple severity curves have different
recovery time intervals for each ischemic time interval. FIG. 5
illustrates a diagram with multiple such severity curves. Each such
severity curve 20 has an associated ischemia severity
classification representative of the ischemic status for different
pairs of T.sub.i, T.sub.r. As is seen in FIG. 5, the ischemia
severity classification typically goes from less sever ischemic
events towards more severe ischemic events when traveling between
the curves 20 along the illustrated arrow. Thus, the more severe
ischemia event, the longer the recovery time interval for a given
ischemia time interval.
[0052] A curve provider 185 is arranged in the ischemia monitoring
system 100 for providing the multiple ischemia severity curves.
This curve provision is preferably implemented by fetching the
respective T.sub.i, T.sub.r values for the curves from the memory
165. These curves can have been pre-defined, e.g. by a physician
and entered or downloaded in the memory 165 using the memory
controller 160. Also patient-specific ischemia severity curves can
be used by the embodiments. In such a case, each time the time
processor 140 determines a pair of T.sub.i, T.sub.r following
detection of an ischemic event, the ischemic event is further
assigned an ischemic severity classification, for instance by the
physician. Once the patient has had multiple ischemic attacks,
several T.sub.i, T.sub.r pairs may be determined for different
ischemic severity classifications, thereby forming a data set that
can be used to define the multiple ischemia severity curves.
[0053] It should be noted that in some applications no dedicated
curves need to be drawn or analyzed. In clear contrast, a set of
T.sub.i, T.sub.r pairs is together defined as constituting or
forming an ischemia severity group or curve having an assigned
ischemia severity classification. Multiple such sets of T.sub.i,
T.sub.r are then stored in the memory 165.
[0054] A curve or group identifier 180 is also arranged in the
ischemia monitoring system 100 in this embodiment for identifying
an ischemia severity curve or group provided by the curve or group
provider 185. This identification is furthermore performed based on
the T.sub.i, T.sub.r pair determined by the time processor 140 for
the detected and now lapsed ischemic event. The status processor
150 determines the ischemic status of the subject based on the
ischemia severity classification assigned to the ischemia severity
curve or group identified by the curve identifier 180.
[0055] FIG. 5 graphically illustrates this curve identification by
plotting, together with the multiple ischemia severity curves, a
determined T.sub.i, T.sub.r pair. The curve 20 that is closest to
the coordinate defined by the T.sub.i, T.sub.r pair is identified
and the ischemia severity classification assigned to this curve 20
is used by the status processor 150 for the purpose of determining
the ischemia status of the subject. The curve identification could
be implemented by identifying the curve 20 that minimizes the
Euclidean distance between the T.sub.i, T.sub.r coordinate and a
point on the curve 20.
[0056] An alternative embodiment is illustrated in the diagram of
FIG. 13. In this embodiment, the ischemia monitoring system 100 has
access to predefined threshold values T.sub.i.sup.1-3,
T.sub.r.sup.1,2 associated with different ischemic severity
classifications. These thresholds have been illustrated in FIG. 13
and defines, in the T.sub.i, T.sub.r plane, different sub-regions
having different ischemic severity classification. As is
illustrated in the figure, previously recorded T.sub.i, T.sub.r
have mainly been present in the sub-region in which
T.sub.i.sup.1.ltoreq.T.sub.i<T.sub.i.sup.2 and
T.sub.r.sup.1.ltoreq.T.sub.r<T.sub.r.sup.2. The three ischemic
events resulting in the three T.sub.i, T.sub.r value pairs present
in this sub-region therefore has a same ischemia severity
classification. However, a subsequent ischemic event results in
significantly prolonged recovery period and ischemic period and
therefore falls within another sub-region,
T.sub.i.sup.2.ltoreq.T.sub.i<T.sub.i.sup.3 and
T.sub.r.sup.21.ltoreq.T.sub.r. This latter ischemic event is
consequently assigned another ischemia severity classification by
the status processor 150 in the ischemia monitoring system.
[0057] The threshold values used to define the different
sub-regions are stored in the memory 165 and are preferably defined
by a physician and entered by him/her in the memory 165. Also
patient-specific thresholds can be defined if the patient has
suffered from multiple previous ischemic events that have been
classified as disclosed herein. In such a case, these prior
classifications and the determined T.sub.i, T.sub.r values can be
used to generate the necessary information, i.e. thresholds, to
define the sub-regions with different ischemia severity
classification.
[0058] The respective numbers of thresholds illustrated in FIG. 13
should merely be seen as an illustrative but non-limiting
example.
[0059] The embodiments of the ischemia monitoring system 100
illustrated in FIGS. 1 and 2 may optionally further comprise an
activity level sensor 190. There are several different activity
sensors 190 known in the art that can be used according to the
embodiments. For instance, accelerometers, motion transducers,
including piezo-based transducers, heart rate sensors, respiratory
rate sensors, respiratory depth sensor etc. can be used and are all
well-known in the art. The activity sensor 190 is preferably
arranged for estimating an activity level of the subject at least
partly during the ischemic event and/or during the following
recovery period. For instance, the activity sensor 190 can be
arranged for determining the activity level of the subject in
connection with at least one of the ischemia onset detector 110
detecting the onset of the ischemic event, the ischemia end
detector 120 detecting the end of the ischemic event and the
recovery end detector 130 detecting the end of the recovery from
the ischemic event.
[0060] The activity level data determined by the activity sensor
190 is either entered in the memory 165 or is directly forwarded to
the status processor 150. In either case, the status processor 150
uses this activity data together with the ischemic time interval
and the recovery time interval in order to determine the ischemic
status of the subject. Usage of activity data in connection with
the time and recovery time intervals may lead to more accurate
status determination and, in particular, to detecting significant
deteriorations in the ischemic burden of the subject. The reason
for this is that at a high activity level, there is a large oxygen
demand by the myocardium. This large oxygen demand might not be
fully supplied due to a cardiovascular disease, such as
atherosclerosis, thereby causing the initiation of an ischemic
event for at least a part of the heart. If the subject, however,
would not have been exercised or otherwise have had such high
activity, the ischemic event might not have occurred or would have
been milder. Furthermore, an ischemic event and following recovery
period resulting in a particular pair of T.sub.i, T.sub.r is
generally regarded as being more severe if the activity level of
the subject is normal or low as determined by the activity sensor
190 when compared to an ischemic event leading to the same pair of
T.sub.i, T.sub.r but during a period of high patient activity.
Thus, the status processor 150 preferably utilizes the activity
level data together with T.sub.i, T.sub.r in the ischemic status
determination or at least preferably notifies and stores the
average patient activity during the ischemic and/or recovery
periods and in particular the ischemic periods together with the
T.sub.i, T.sub.r data.
[0061] The units 110 to 190 of the ischemia monitoring system 100
may be implemented in hardware, software or a combination of
hardware and software. The ischemia monitoring system 100 may be
implemented in an implantable medical device or in a
non-implantable data processing device, such as a computer or
computer system, as is further described herein. A distributed
implementation is also possible with some of the units implemented
in a first device, such as an implantable medical device, and with
the other units provided in a second device, such as programmer,
capable of conducting wired or wireless communication with the
first device. For instance, the ischemia onset detector 110,
ischemia end detector 120, recovery end detector 130 and optionally
the time processor 140 can be arranged in the first device with the
remaining units, possibly excluding the optional activity sensor
190, arranged in the second, non-implanted device.
[0062] FIG. 3 is a schematic overview of a human patient 1 having
an implantable medical device (IMD) 200. In the figure, the IMD 200
is illustrated as a device that monitors and/or provides therapy to
the heart 10 of the patient 1, such as a pacemaker, cardiac
defibrillator or cardioverter. The IMD 200 is, in operation,
connected to one or more, two in the figure, cardiac leads 250, 260
inserted into different heart chambers, the right atrium and the
right ventricle in the figure, or being epicardially positioned
relative the heart 10. The IMD 200 must not necessarily be
connected to two cardiac leads 250, 260 but could alternatively be
connected to a single lead 260 carrying at least one electrode or
more than two cardiac leads 250, 260.
[0063] FIG. 3 also illustrates an external programmer or
clinician's workstation 300 that can communicate with the IMD 200.
As is well known in the art, such a programmer 300 can be employed
for transmitting IMD programming commands, using an included
transmitter (not illustrated), causing a reprogramming of different
operation parameters and modes of the IMD 200. Furthermore, the IMD
200 can upload diagnostic data descriptive of different medical
parameters or device operation parameters collected by the IMD 200
to a receiver (not illustrated) of the programmer 300. Such
uploaded data may optionally be further processed in the programmer
300 before display to a clinician on a connected display screen
320.
[0064] In a particular embodiment, the ischemia monitoring system
100 such as disclosed in FIG. 1 or 2 can be implemented or at least
partly implemented in the programmer 300 or indeed in another
non-implantable data processing device. In such a case, the
ischemia monitoring system 100 can receive data input allowing the
including units to identify ischemia onset, end and recovery end.
This input can be affected by a general input and output (I/O) 310
of the data processing device 300. This means that the I/O 310
could be connected to further equipment that can be used for the
purpose of collecting data that can be processed by the ischemia
onset detector, ischemia end detector and/or the recovery end
detector. Alternatively, the I/O 310 is a so-called user I/O 310
that can be utilized by a user, such a physician, for manually
inputting data that are processed by the ischemia monitoring system
100 for ultimately determining the ischemia time interval and the
recovery time interval.
[0065] Herein follows more detailed examples of how the ischemia
and recovery time intervals can be determined using non-implantable
devices. These devices can therefore constitute a part of the data
processing device, be connected thereto for automatic or
user-triggered transfer of data or be separate from the data
processing device, in which case a user needs to manually input to
using the user I/O 310.
[0066] A preferred technique for determining the ischemia time
interval is to use a surface electrogram (ECG) and in particular
through ST segment analysis of such surface ECG. The technique
involves recording a surface ECG during at least one cardiac cycle,
preferably of multiple consecutive cardiac cycles. In the latter
case, one or more of these multiple consecutive cardiac cycles can
be investigated further as disclosed herein. Alternatively, an
average cardiac cycle is first generated based on the multiple
consecutive cardiac cycles in order to reduce the impact of
spontaneous deviations, noise and other interfering sources.
[0067] The so-called R wave of a QRS complex in a (average) heart
cycle is identified, preferably as corresponding to the ECG value
having the largest absolute value. A time window following the
localized R wave in the cardiac cycle is defined. This time window
should cover the ST segment and preferably the T wave of the heart
cycle. For a human with a normal heart rate, this time window is
typically 50-300 ms after the R wave. However, depending on the age
and activity level of the subject, among others, the size and
location of the time window can be different. The T wave can be
identified as corresponding to a local max (in the case of normal
ECG) following the end of the QRS complex.
[0068] FIGS. 7A to 7D schematically illustrate surface ECG of a
portion of a heart cycle, clearly depicting the QRS complex and the
P and T waves. FIG. 7A is the ECG from a healthy heart. FIGS. 7B
and 7C illustrate two versions of ST segment depletions that have
occurred in an ischemic heart. In FIG. 7D, the ischemic heart
presents a T wave inversion on the recorded surface ECG.
[0069] The ECG level in the measurement window, i.e. the ST segment
and the T wave, is measured. This ECG level can be any parameter
representative of the ECG level in the measurement window. A
non-limiting example is the averaged value in the measurement
window.
[0070] This parameter is then compared with a reference parameter,
which preferably corresponds to the ECG level in the measurement
window during one or more heart cycle with normal, non-ischemic
condition of the patient. The reference parameter is therefore
advantageously determined in connection with a patient visit at a
physician and then stored in the ischemia monitoring system for
later use.
[0071] The calculated parameter is compared to the reference
parameter and if there is a significant difference there between,
the ischemia onset detector detects the onset of an ischemic event.
The ischemia end detector correspondingly detects the end of the
ischemic event once there is no longer any significant difference
between the calculated parameter and the reference parameter. In
order to reduce the risk of misinterpreting naturally varying
parameter differences for ischemia-triggered parameter differences,
the ischemia onset detector could be configured for detecting the
ischemia event onset only if the respective calculated parameters
for multiple, preferably consecutive, heart cycles differ
significantly from the reference parameter. Correspondingly, the
ischemia end detector can be configured for detecting the end of
the ischemic event only if the respective calculated parameters for
multiple, preferably consecutive, heart cycles no longer differ
significantly from the reference parameter.
[0072] In an alternative embodiment, no parameter representative of
the ECG level in the measurement window is determined. In clear
contrast, the complete ECG waveform of the ECG signal in the
measurement window is extracted. The extracted ECG waveform is then
compared to a reference ECG waveform recorded from the subject
during one or multiple heart cycles during normal, non-ischemic
condition. The ECG waveform and the reference ECG waveform are
compared using any type of curve or pattern comparing technique for
the purpose of detecting any significant difference. For instance,
the absolute difference or the squared difference between
respective ECG samples in the ECG waveform and the reference ECG
waveform can be summed and compared to a pre-defined threshold. If
the summed absolute or squared differences exceed the threshold, a
significant change is detected corresponding to a detected onset of
an ischemic event. Correspondingly, once the absolute or squared
differences no longer exceed the threshold, the end of the ischemic
event is detected.
[0073] The recovery time interval is advantageously determined from
sensor data capturing the mechanical behavior of the heart. A
typical example of suitable sensor is a pulse oximeter registering
the blood pressure or photoplethysmograph sensor measuring volume
changes and can be used for monitoring blood pressure. Other
sensing techniques that can monitor the blood pressure could
alternatively be used.
[0074] In a typical setting, a heart cycle is identified from the
plethysmogram, such as the portion of the plethysmogram between two
consecutive R waves. This identified waveform is compared to a
reference waveform determined for the patient during normal,
non-ischemic condition. The photoplethysmograph sensor is
preferably automatically or manually activated once the end of the
ischemic period has been detected as described above. In such a
case, the mechanical pumping of the heart is monitored by
comparisons of the plethysmogram data with the reference waveforms
until there no longer is any significant difference between the
plethysmogram waveform and the reference waveform. This point in
time corresponds to the end of the recovery period when the
mechanical behavior of the heart has been restored.
[0075] The data processing device embodying the ischemia monitoring
system can therefore advantageously be connected to a surface ECG
recording unit and a plethysmograph sensor in order to provide
input data to the ischemia monitoring system for the purpose of
identifying the ischemia and recovery onset and end times.
Alternatively, the recorded ECG data and plethysmogram data can be
input to the data processing device by a user to then be analyzed
by the ischemia monitoring system.
[0076] FIG. 4 is a schematic block diagram of an IMD 200 according
to an embodiment. The IMD 200 has a lead or electrode connecting
arrangement 210 represented by a lead input/output (I/O) 210 in the
figure.
[0077] This lead I/O 210 is, in operation, connectable to multiple
electrodes 252, 254, 262, 264 of which at least one is designed for
being implanted in or at least in connection with the heart. As a
consequence, at least one of the multiple electrodes 252, 254, 262,
264 is arranged on a cardiac lead 250, 260 connectable to the lead
I/O 210. This further implies that at least one but not all of the
multiple electrodes 252, 254, 262, 264 may not necessarily be
lead-arranged or be implanted in the immediate vicinity of the
heart. An example of such an electrode, is an electrode
constituting the whole or a portion of the case or can of the IMD
200.
[0078] As is well known in the art, an implantable lead or catheter
250, 260 has a proximal end connectable to the IMD 200 through the
lead I/O 210. This IMD-connecting end presents one or more electric
terminals that are in electric connection with the electrodes 252,
254, 262, 264 present on the opposite distal lead end, where the
electric connection is achieved by electric conductors running
along the length of the lead body. The distal lead end with its
electrodes 252, 254, 262, 264 is then provided in connection with
the heart tissue. For this purpose, the lead 250, 260 can include a
tissue anchoring element, such as a helical fixation element,
though other fixation elements, such as passive fixation elements,
including fines, tines, etc., are also common. The fixation element
can indeed constitute one of the electrodes of the lead 252, 262,
while remaining electrodes can be ring electrodes 254, 264 often
denoted indifferent electrodes in the art, defibrillation
electrode, or the like.
[0079] The IMD 200 is connected to at least one implantable cardiac
lead 250, 260. The cardiac lead 250, 260 can be an intracardiac
lead positioned in any of the chambers of the heart, such as right
and/or left atrium and/or ventricle. Alternatively, the lead 250,
260 could be epicardially positioned relative the heart, such as in
the coronary vein. In the case of multiple connectable leads 250,
260 the IMD 200 can be connected to multiple intracardiac or
endocardial leads, multiple epicardial leads or a combination of
intracardial and epicardial leads. Generally, in a single-chamber
bradycardia device 200 a single cardiac lead 250 is implanted in
the right ventricle of the heart. Correspondingly, in a
dual-chamber cardiac resynchronization defibrillator, a respective
cardiac lead is typically implemented in the right atrium, the
right ventricle and epicardially relative the left ventricle.
[0080] In an embodiment, the IMD 200 includes the ischemia
monitoring system 100 or at least a portion thereof as previously
mentioned.
[0081] In an embodiment, the IMD 200 includes an intracardiac ECG
(IECG) processor 220 arranged connected to the lead I/O 210 and
arranged for generating IECG data based on electric signals
collected from the heart by the electrodes 252, 254, 262, 264. The
IECG data can then be analyzed by the ischemia onset detector and
ischemia end detector as described above in the case of a surface
ECG for the purpose of detecting the start and end of an ischemic
event based on ST segment deviations.
[0082] In a particular embodiment, if the IMD 200 is connectable to
one or more leads 250, 260 together having multiple electrodes 252,
254, 262, 264 implanted in or in connection with the heart,
multiple separate IECGs can be recorded by the IECG processor 220
for different pairs of the electrodes 252, 254, 262, 264 and/or for
different combinations of a case electrode and the
cardiac-implanted electrodes 252, 254, 262, 264. These multiple
IECGs are then co-processed by the IECG processor 220 for the
purpose of calculating a pseudo-global IECG for the heart. This
co-processing can be conducted by calculating an average of the
multiple unipolar IECGs and/or the bipolar IECGs. The pseudo-global
IECG provides a more global electrical fingerprint of the heart as
compared to individual IECG that more reflects the local electric
activity in a portion of the heart. It is expected that global
electrical activity is more valuable for the purpose of ischemia
detection and the determination of the ischemic time interval.
[0083] The detection of the onset and end of the ischemic time
interval is then basically performed in the same way as for the
surface ECG with the exception that the IECG or pseudo-global IECG
is processed by the ischemia onset and end detectors instead of the
surface ECG.
[0084] Recording of multiple IECGS and the generation of a
pseudo-global IECG is not mandatory for the purpose of detecting
the onset and end of the ischemic time interval by an IMD 200. In
particular local ischemia monitoring in selected parts of the heart
can benefit from using one or more individual IECGs representative
of the local electrical activity of the heart over time in the
selected parts.
[0085] If the IMD 200 is connected to a single lead 250, the number
of cardiac electrodes can be more limited and therefore recorded
IECGs could be more local as compared to an IMD 200 having two or
more connected leads 250, 260. In such a case, generated IECGs from
the IECG processor 220 can be further processed for the purpose of
synthesizing or emulating a surface ECG from the IECGs. Techniques
for such surface ECG emulation from IECGs are disclosed in the U.S.
Pat. No. 6,813,514 the teaching of which regarding surface ECG
emulation is hereby incorporated by reference. Briefly, the
technique is based on inputting electrical cardiac signals sensed
using a combination of pairs of electrodes implanted within the
patient and then emulating each of a plurality of separate signals
associated with a multiple-lead surface ECG of a patient based on
the input electrical cardiac signals. By emulating each of the
individual signals of the surface ECG rather than merely generating
a combined surface ECG, the separate signals can be individually
processing using a wide variety of techniques, such as filtering
the individual signals separately.
[0086] The emulated surface ECG can then be used by the ischemia
monitoring system 100 in similarity to the above disclosed measured
surface ECG for the purpose of detecting onset and end of an
ischemic event based on ST-deviations in the surface ECG.
[0087] In a preferred embodiment, the IMD 200 has a signal
generator 230 electrically connected to the lead I/O 210 and
connectable electrodes 252, 254, 262, 264. The generator 230
generates an electric signal. The electric signal is an alternating
current (AC) signal having particular frequency or frequencies. The
electric signal is applicable over at least a portion of a heart in
a subject by two electrodes 252, 254 of the multiple connectable
electrodes 252, 254, 262, 264.
[0088] In operation, the signal generator 230 generates the
electric signal having a defined time-dependent voltage/current
profile and forwards the signal to the lead I/O 210. The lead I/O
210 directs the electric signal to the two relevant signal applying
electrodes 252, 254 to apply the signal over the relevant portion
of the heart. Two electrodes 252, 254 of the multiple connected
electrodes 252, 254, 262, 264 collect a resulting electric signal,
i.e. resulting AC signal, originating from at least the portion of
the heart. This resulting signal is due to the applied electric
signal from the signal generator 230. In the case multiple electric
signals where generated by the signal generator 230 and applied
over different portions of the heart, a respective resulting
electric signal is preferably collected by respective electrode
pairs for each of the applied electric signals.
[0089] An impedance processor 240 is electrically connected to the
signal generator 230 and the lead I/O 210. The impedance processor
240 processes the electric signal generated by the signal generator
230 and the resulting electric signal collected by the two
electrodes 252, 254 connected to the lead I/O 210. In more detail,
the processor 240 calculates cardiogenic impedance data or signal
based on the generated electric signal, such as based on the
current of the electric signal, and the resulting electric signals,
e.g. based on the measured voltage of the resulting electric
signal. This impedance data is reflective of the mechanical
function of at least a portion of the heart and more preferably
representative of the mechanical pumping action of the heart.
[0090] This cardiogenic impedance data is processed by the ischemia
monitoring system for the purpose of detecting the end of the
recovery period. This detection is possibly as any mechanical
dysfunction of the heart caused by the ischemic event and present
during the recovery period can efficiently be picked up by the
cardiogenic impedance. Thus, during the recovery period, the
cardiogenic impedance reflective of the mechanical heart function
is significantly different from the cardiogenic impedance during
normal, non-ischemic/recovery periods.
[0091] In a typical implementation, a complete heart cycles is
identified in the impedance data, such as between two consecutive R
waves. The waveform or set of impedance samples of this portion of
the impedance signal is analyzed with a corresponding waveform or
set of impedance samples previously recorded during a period of
normal non-ischemic and non-recovery operation. A waveform or data
set comparison is then conducted as previously described for the
purpose of detecting a significant difference between the
waveform/set and a reference waveform/set, which difference is
present during the recovery period. Once the heart function, i.e.
pumping action, as been restored, corresponding to the end of the
recovery period, the recovery end detector determines that there is
no longer any significant difference between a waveform/set and the
reference waveform/set or there is no such significant difference
for multiple consecutive waveforms/sets and the reference
waveform/set.
[0092] In a preferred embodiment, the waveform/set of impedance
samples not necessarily corresponds to a compete heart cycle. In
clear contrast, the waveform/set of impedance samples preferably
corresponds to the diastolic phase, or a portion thereof, of the
heart cycle. It has been concluded that this part of the heart
cycles is particularly sensitive for registering changes in the
cardiogenic impedance signals originating from mechanical
dysfunction of the heart following an ischemic event. Therefore,
the diastolic part of the impedance waveform or data set is
preferably compared to the reference waveform or data set.
[0093] In the case systolic variables are easier to measure the
waveform/set of impedance samples could instead correspond to the
systolic phase, or a portion thereof, of the heart cycle.
[0094] The IMD 200 advantageously comprises or is connectable to a
posture sensor (not illustrated) for determining a current posture
of the subject. Such posture sensors adapted for implementation in
an IMD 200 are well-known in the art. There is actually combined
position and activity sensor available. Such a combined activity
and posture sensor is then preferably used in order to obtain not
only activity data but also posture data but without the drawback
of having extra dedicated sensor equipment in the IMD 200. The
subject posture determined by the (activity and) posture sensor is
preferably collected in connection with determining the recovery
time interval, in particular if an impedance-based technique is
used for the recovery time interval determination. The cardiogenic
impedance is generally partly affected by the current body posture,
resulting in different cardiogenic impedance waveforms for a
standing body posture as compared to a subject lying down, even
though the same impedance vector has been used. The impedance-based
recovery time interval determination is therefore preferably
coordinated and associated with posture data from the posture
sensor. In such a case, a set of multiple reference parameters or
reference recovery time parameters can be available for different
body postures, such as one for a standing body and one for a
reclining body. The posture data is then used in order to select
the particular reference parameter(s) to use when comparing the
determined ischemic and recovery time intervals with the reference
parameter(s) for the purpose of determining the ischemic status and
detecting any significant change thereof. The inclusion of body
posture data in the determination of the ischemic status further
increases the specificity and accuracy in the determination and
thereby provides an improved ischemic status determination and
monitoring.
[0095] The IMD 200 may optionally include an alarm unit 270 capable
of sounding an alarm signal or providing a tactile alarm signal.
This alarm unit 270 is responsive to the ischemia monitoring system
100 and more particularly to the status processor detecting a
deterioration in the ischemic status of the subject as previous
described. This alarm will alert the subject of the lapsed ischemic
event and urge him/her to contact his/her physician and/or take
suitable anti-ischemic medicament, such as nitrates, beta-blockers,
calcium channel blockers, aspirin, etc. In addition, or
alternatively, the alarm unit 270 or some other unit in the IMD 200
may generate an alarm signal that is automatically uploaded to an
external communication unit, such as home monitor, mobile
telephone, personal digital assistant, computer, or other unit
capable of wirelessly receiving data from the IMD 200. This
external unit may optionally display a warning message on a display
screen informing the IMD patient of the detected deterioration in
ischemic status. Furthermore, or instead, the external unit
forwards the alarm signal to the physician using a computer
network, telephone network or a radio-based wireless communication
network.
[0096] The IMD 200 may optionally include a so-called treatment
unit 280 arranged connected to the lead I/O 210 for generating
electric treatment signals or pulses to a portion of the heart
using electrodes 252, 254, 262, 264 of the at least one connectable
lead 250, 260. The treatment unit 280 generates the electric
treatment signal according to a treatment scheme, defining the
duration of the electric treatment pulses, the timing thereof and
other characteristics of the electric treatment signal.
[0097] The treatment unit 280 is preferably connected to and
controlled by a treatment controller 285. This treatment controller
285 can, for instance, trigger the treatment unit 280 to start
generating a particular electric treatment signal, switch to
another treatment scheme to use for the purpose of generation and
application of the electric treatment signals and/or adjust
particular settings, such a pulse duration, timing, pulse
magnitude, etc.
[0098] In a particular embodiment, the treatment controller 285 is
responsive to the ischemia monitoring system 100 and implemented
for controlling the operation of the treatment unit 280 based on
the detection of a change in the ischemic status of the subject as
determined by the status processor of the ischemia monitoring
system 100. The treatment controller 285 is advantageously arranged
for selecting an anti-ischemia treatment scheme or adjusting a
treatment scheme currently used by the treatment unit 280 based on
the detection of a deterioration of the ischemic status of the
subject. A preferred such anti-ischemia treatment scheme adjustment
is to reduce the maximum tracking rate of the treatment unit 280 to
thereby reduce the pacing rate. A reduced pacing rate (ventricular
contraction rate) will improve the coronary perfusion, which in
turn improves the ischemic status.
[0099] Other anti-ischemia treatment actions could alternatively,
or in addition, be triggered by the treatment controller 285, such
as the release of anti-thrombotic agent if the IMD 200 includes
equipment for allowing a controlled release of such agents.
[0100] The units 100, 210-240, 270-285 of the IMD 200 may be
implemented in hardware, software or a combination of hardware and
software. In FIG. 4 and the discussion of embodiments above,
reference has only been to the IMD unit directly involved in the
present invention. It is therefore expected according to the
invention that the IMD 200 will typically include other units and
functionalities required for efficient and correct operation of the
IMD 200.
[0101] The present embodiments are not limited to the above
presented techniques for detecting the onset and end of the
ischemia event and recovery period. In clear contrast, other
techniques known in the art for detecting ischemia onset and end
and recovery onset and end can of course be used in connection with
the present embodiments. For instance, biochemical markers, such as
Troponin I/T, NT-proBNP and local potassium leakage can be used for
ischemia time interval determination. Correspondingly, other
techniques for monitoring the mechanical function of the heat, such
as recovery of left ventricular diastolic pressure (LVDP), left
atrial pressure (LAP), pulmonary arterial oxygen saturation can be
used for the purpose of recovery time interval determination.
[0102] In the brain, the ischemic time interval can be determined
from blood pressure measurements with a blood pressure sensor.
Alternatively, blood and tissue oxygen changes detected by oxygen
sensors can be used. The following recovery time interval is
advantageously determined from electroencephalography (EEG)
measurements. Detection of the end of the recovery period is then
identified based on waveform analysis between recorded EEG waveform
and a reference waveform in similarity to (I)ECG analysis.
[0103] FIG. 8 is a flow diagram illustrating an ischemia monitoring
method according to an embodiment. The method generally starts in
step S1, which investigates whether an ischemic event is detected.
If such an even is detected the method continues to step S2, where
the start time T.sub.i.sup.st of the ischemic event is stored or an
ischemia trigger is started. A next step S3, typically
periodically, investigates whether the detected ischemic event has
ended, thereby continuing the method to step S4. Step S4 calculates
the ischemic time interval of the ischemic event based on the
stored start time T.sub.i.sup.st and an end time T.sub.i.sup.e,
T.sub.i=T.sub.i.sup.e-T.sub.i.sup.st. Alternatively, the ischemic
time interval is obtained by reading the now stopped ischemia
trigger. Step S4 optionally also initiates a recovery timer.
[0104] A next step S5 investigates whether the following recovery
period has ended. A detected recovery end triggers a next step S6
to determine a recovery time interval based on the determined end
time T.sub.r.sup.e of the recovery period and the end time of the
ischemic event, T.sub.r=T.sub.r.sup.e-T.sub.i.sup.e. Alternatively,
the now stopped recovery timer is read to get the recovery time
intervals.
[0105] The two determined time intervals are preferably stored in
step S7 and co-processed in step S8 for monitoring the ischemic
status of the subject as previously described.
[0106] The method then ends or returns to step S1 for detecting a
further potential ischemic event of the subject's heart, which is
schematically illustrated by the line L1.
[0107] FIG. 9 is a flow diagram illustrating an additional,
optional step of the ischemia monitoring method. The method
continues from step S7 of FIG. 8. A next step S10 calculates a
statistical distribution of the currently determined ischemia and
recovery time interval pair together with corresponding time
interval pairs determined for previously detected ischemic events
of the subject's heart. The calculated statistical distribution,
typically represented in the form of mean values and standard
deviations is compared in step S8 of FIG. 8 with a corresponding
reference statistical distribution and its reference mean values
and standard deviations as previously described.
[0108] FIG. 10 is a flow diagram illustrating another optional step
of the ischemia monitoring method applicable in the case multiple
so-called ischemia severity curves are available and representing
the recovery time interval as a function of ischemic time interval
for different ischemia severity levels. The method then continues
from step S7 of FIG. 8. A next step S20 identifies one of the
multiple ischemia severity curves based on the determined ischemia
and recovery time intervals. The ischemia severity classification
assigned to the ischemia severity curve identified as being most
relevant for the current time interval pair is used in step S8 of
FIG. 8 for monitoring the ischemic status of the subject and
preferably for detecting any change in the ischemic status.
[0109] FIG. 11 is a flow diagram illustrating an additional,
optional step of the ischemia monitoring method. The method
continues from step S6 of FIG. 8, with the next step S30
determining an activity level of the subject in addition to the
determination of the time interval pair. The activity level data is
preferably stored together with the time interval data in step S7
of FIG. 8 and used with the time interval data for the ischemic
status monitoring as described herein.
[0110] FIG. 12 is a flow diagram illustrating an embodiment of the
ischemic status monitoring step S8 of FIG. 8 in more detail. The
method continues from step S7 in FIG. 8. A next step S40 detects a
deterioration in ischemic status of the subject based on the
ischemic and recovery time intervals and optionally the activity
level data. In response to this deterioration the following
optional step S41 activates an alarm informing the subject or
his/her physician of the detected deterioration. In the implanted
embodiment, the alarm can be a tactile or audio alarm or trigger an
automatic upload of an alarm signal to an external communication
unit, such as a home monitor, which in turn can forward the alarm
signal to the physician using a computer network, telephone network
or a radio-based wireless communication network.
[0111] In addition to or instead of running an alarm in step S41,
an anti-ischemia treatment is triggered in step S42 in response to
the deterioration detection. This treatment trigger is preferably
an automatic trigger, which can, for instance, initiate delivery of
anti-ischemic electric treatment pulses, an adjustment of the
operation characteristics or functions of an IMD and/or the release
of anti-thrombotic and/or other anti-ischemic agents from the
IMD.
[0112] The embodiments described above are to be understood as a
few illustrative examples of the present invention. It will be
understood by those skilled in the art that various modifications,
combinations and changes may be made to the embodiments without
departing from the scope of the present invention. In particular,
different part solutions in the different embodiments can be
combined in other configurations, where technically possible. The
scope of the present invention is, however, defined by the appended
claims.
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